Low levels of progesterone and derivatives in cerebrospinal fluid of patients affected by status epilepticus

Neurosteroids such as allopregnanolone may play a role in epilepsy as positive modulators of inhibitory currents mediated by γ‐aminobutyric acid type A ( GABA A ) receptor. Indeed, these molecules have been consistently shown to be anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated neurosteroids in the cerebrospinal fluid ( CSF ) of patients with status epilepticus ( SE ) by liquid chromatography tandem‐mass spectrometry. Patients were retrospectively identified within subjects who received a lumbar puncture in the 2007–2017 period. Seventy‐three patients (median age 65, ranging from 13 to 94 years; 67% women) with SE were evaluated. Controls ( n  = 52, median age 53, ranging from 16 to 93 years; 65% women) were patients presenting with symptoms for which a lumbar puncture was required by clinical guidelines, and who were negative at the end of the diagnostic work‐up. Progesterone was 64% lower in patients with SE ( p  <   0.001). With respect to progesterone, upstream pregnenolone sulfate and pregnenolone did not change. Instead, downstream 5α‐dihydroprogesterone, pregnanolone and allopregnanolone were, respectively, 49% ( p  <   0.001), 21% ( p  <   0.01) and 37% ( p  <   0.001) lower than in controls. Duration or type of SE , age and sex did not consistently affect CSF neurosteroid levels in the SE cohort. Instead, pregnenolone sulfate (Spearman's ρ = 0.4335, p  <   0.01), allopregnanolone (ρ = 0.4121, p  < 0.05) and pregnanolone (ρ = 0.592, p  <   0.001) levels significantly increased by aging in controls. We conclude that neurosteroidogenesis is defective in patients with SE .